Improved survival with combined gemcitabine and S-1 for locally advanced pancreatic cancer: pooled analysis of three randomized studies

Background The long-term prognosis for localized pancreatic cancer (PC) remains poor. Three randomized trials (GEST phase III, JACCRO PC-01 phase II and GEMSAP phase II) evaluated gemcitabine (Gem) with or without S-1 for patients with metastatic and locally advanced PC. A pooled analysis based on published data examined whether Gem with S-1 (GS) is superior to Gem alone in overall survival (OS) in patients with locally advanced PC. Methods Data were extracted on 193 patients: 31 (JACCRO), 28 (GEMSAP), and 134 (GEST). OS was used for primary endpoint and progression-free survival (PFS) was used for secondary endpoint. A general variance-based method was used to estimate the pooled HR and 95% CI between GS (n = 96) and Gem (n = 97). Results Meta-analysis demonstrated that the overall risk of death was significantly different between the two chemotherapies (hazard ratio = 0.673, 95% confidence interval: 0.488-0.929, P = 0.016). The median PFSs for GS and GEM in the JACCRO, GEMSAP, and GEST studies were 12.0, 12.6, and 10.7 months, and 4.1, 8.1, and 6.2 months, respectively (P = 0.001). The random-effect pooled estimate for 165 patients showed the objective response rate (ORR) in the GS group (28.4%) was better in the Gem group (8.3%, P = 0.001). Conclusions GS improved ORR, PFS and OS in patients with locally advanced PC over Gem alone. GS could become one of the front-line chemotherapeutic agents.